Product Validation and Stability Testing of Pharmacy Compounded Cholic Acid Capsules for Dutch Patients with Rare Bile Acid Synthesis Defects.

Bile acid synthesis defects (BASDs) comprise a group of rare diseases that can be severely disabling. Bile acid supplementation with 5 to 15 mg/kg cholic acid (CA) has been hypothesized to decrease endogenous bile acid production, stimulate bile secretion, and improve bile flow and micellar solubilization, thereby improving the biochemical profile and potentially slowing down disease progression. Currently, CA treatment is unavailable in the Netherlands, and CA capsules were compounded by the Amsterdam UMC Pharmacy from CA raw material.

Pre-Operative Decitabine in Colon Cancer Patients: Analyses on WNT Target Methylation and Expression.

DNA hypermethylation is common in colon cancer. Previously, we have shown that methylation of WNT target genes predicts poor prognosis in stage II colon cancer. The primary objective of this study was to assess whether pre-operative treatment with decitabine can decrease methylation and increase the expression of WNT target genes , and in colon cancer patients.

Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects.

Intake of a high-fat meal induces a systemic inflammatory response in the postprandial which is augmented in obese subjects. However, the underlying mechanisms of this response have not been fully elucidated. We aimed to assess the effect of gut microbiota modulation on postprandial inflammatory response in lean and obese subjects.

The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy.

Introduction: Currently, no therapies are available for Zellweger spectrum disorders (ZSDs), a group of genetic metabolic disorders characterised by a deficiency of functional peroxisomes. In a previous study, we showed that oral cholic acid (CA) treatment can suppress bile acid synthesis in ZSD patients and, thereby, decrease plasma levels of toxic C -bile acid intermediates, one of the biochemical abnormalities in these patients. However, no effect on clinically relevant outcome measures could be observed after 9 months of CA treatment.

Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial.

Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol.

Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial.

In experimental models, mesenchymal stem cells (MSCs) can modulate various immune responses implicated in the pathogenesis of sepsis. Intravenous injection of lipopolysaccharide (LPS) into healthy subjects represents a model with relevance for the host response to sepsis. To explore the use of MSCs in sepsis, we determined their effect on the response to intravenous LPS in a randomized study in 32 healthy subjects with four treatment arms: placebo or allogeneic adipose MSCs (ASCs) intravenously at either 0.

Pulmonary challenge with carbon nanoparticles induces a dose-dependent increase in circulating leukocytes in healthy males.

Background: Inhalation of particulate matter, as part of air pollution, is associated with increased morbidity and mortality. Nanoparticles (< 100 nm) are likely candidates for triggering inflammatory responses and activation of coagulation pathways because of their ability to enter lung cells and pass bronchial mucosa. We tested the hypothesis that bronchial segmental instillation of carbon nanoparticles causes inflammation and activation of coagulation pathways in healthy humans in vivo.

Cholic acid therapy in Zellweger spectrum disorders.

Introduction: Zellweger spectrum disorders (ZSDs) are characterized by a failure in peroxisome formation, caused by autosomal recessive mutations in different PEX genes. At least some of the progressive and irreversible clinical abnormalities in patients with a ZSD, particularly liver dysfunction, are likely caused by the accumulation of toxic bile acid intermediates. We investigated whether cholic acid supplementation can suppress bile acid synthesis, reduce accumulation of toxic bile acid intermediates and improve liver function in these patients.

Nutrition before, during, and after surgery increases the arginine:asymmetric dimethylarginine ratio and relates to improved myocardial glucose metabolism: a randomized controlled trial.

Background: Nitric oxide (NO) is essential for the optimal perfusion of the heart and its vasculature. NO may be insufficient in surgical patients because its precursor arginine is decreased, and the inhibitor of NO synthesis asymmetric dimethylarginine (ADMA) is increased. Besides arginine, the presence of other amino acids essential for the proper metabolism of cardiac cells may be decreased too.

Clinical evaluation of vancomycin dosage in pediatric oncology patients.

Vancomycin trough serum concentrations were below therapeutic range (8-15 mg/L) in 58% of 124 pediatric oncology patients receiving 60 mg/kg/d divided qid. Patients <6 and between 6 and 12 years had significantly lower trough concentrations than patients >12 years. A vancomycin dosage of 60 mg/kg/d is inadequate for pediatric oncology patients >12 years.

Posaconazole treatment in hematology patients: a pilot study of therapeutic drug monitoring.

Background: Posaconazole is indicated for prophylaxis and salvage therapy of invasive fungal infections. Based on pharmacokinetic-pharmacodynamic data, minimum serum concentrations for each indication have been proposed, for example, for prophylaxis >0.5-0.

Towards evidence-based pharmacotherapy in children.

In daily practice, it is difficult to find a registered drug for children, because about 70% of the drugs prescribed in children are not studied, off-label or unlicensed in this age group. Clinical trials have usually been performed in adults, and then in daily practice dosages are adjusted for children without proper studies in that age group. In some countries, national formularies are being established to overcome the existing variance in prescribing between physicians.